No abstract

The growing insight into the biological role of hydrogen peroxide (H2O2) under physiological and pathological condition and the role it presumably plays in the action of natural and synthetic redox-active drug imparts a need to accurately define the type and magnitude of reactions which may occur with this intriguing and key species of redoxome. Historically, and frequently incorrectly, the impact of catalase-like activity has been assigned to play a major role in the action of many redox-active drugs most so SOD mimics and peroxynitrite scavengers, and in particular MnTBAP3− and Mn salen derivatives. The advantage of one redox-active compound over another has often been assigned to the differences in catalase-like activity. Our studies provide substantial evidence that Mn(III) N-alkylpyridylporphyrins couple with H2O2 in actions other than catalase-related. Herein we have assessed the catalase-like activities of different classes of compounds: Mn porphyrins (MnPs), Fe porphyrins (FePs), Mn(III) salen (EUK-8) and Mn(II) cyclic polyamines (SOD-active M40403 and SOD-inactive M40404). Nitroxide (Tempol), nitrone (NXY-059), ebselen and MnCl2, which have not been reported as catalase-mimics, were used as negative controls, while catalase enzyme was a positive control. The dismutation of H2O2 to O2 and H2O was followed via measuring oxygen evolved with Clark oxygen electrode at 25°C. The catalase enzyme was found to have kcat(H2O2) = 1.5 × 106 M−1 s−1. The yield of dismutation, i.e. the amount of O2 evolved, was assessed also. The magnitude of the yield reflects an interplay between the kcat(H2O2) and the stability of compounds towards H2O2-driven oxidative degradation, and is thus an accurate measure of the efficacy of an catalyst. The kcat(H2O2) values for 12 cationic Mn(III) N-substituted (alkyl and alkoxyalkyl) pyridylporphyrin-based SOD mimics and Mn(III) N,N’-dialkylimidazolium porphyrin, MnTDE-2-ImP5+ ranged from 23 to 88 M−1 s−1. The analogous Fe(III) N-alkylpyridylporphyrins showed ~10-fold higher activity than the corresponding MnPs, but the values of kcat(H2O2) are still ~4 orders of magnitude lower than that of the enzyme. While the kcat(H2O2) values for Fe ethyl and n-octyl analogs were 830 and 360 M1 s−1, respectively, the FePs are more prone to H2O2-driven oxidative degradation therefore allowing for similar yields in H2O2 dismutation as analogous MnPs. The kcat(H2O2) values are dependent upon the electron deficiency of the metal site as it controls the peroxide binding in the 1st step of dismutation process. SOD-like activities depend upon electron-deficiency of the metal site also, as it controls the 1st step of O2.− dismutation. In turn, the kcat(O2.−) parallels the kcat(H2O2). Therefore, the electron-rich anionic non-SOD mimic MnTBAP3− has essentially very low catalase-like activity, kcat(H2O2) = 5.8 M−1 s−1. The catalase-like activity of Mn(III) and Fe(III) porphyrins are at most, 0.0004% and 0.05% of the enzyme activity, respectively. The kcat(H2O2) of 8.2 and 6.5 M−1 s−1 were determined for elect...

Two dinuclear seven-coordinate manganese(II) complexes containing two pentaazamacrocyclic subunits, with imine or amine functionalities, respectively, have been synthesized and characterized in the solid state as well as in aqueous solutions of different pH, by performing X-ray structure analyses, SQUID, potentiometric, electron spray ionization-mass spectrometry (ESI-MS), electrochemical, and (17)O NMR water exchange measurements (varying temperature and pressure), and by determination of SOD activity. The two manganese(II) centers within the dinuclear structures behave independently from each other and similarly to the manganese centers in the corresponding mononuclear complexes. However, the dinuclear amine complex possesses increased complex stability and acidity of the coordinated water molecules (pK(a2) = 8.92) in comparison to the corresponding mononuclear analogue. This allowed us to observe a stable trans-aqua-hydroxo-Mn(II) species in an aqueous solution and to study for the first time the trans-effect of the hydroxo group on the water lability on any divalent metal center in general. The observed trans-labilizing effect of the hydroxo ligand is much smaller than in the case of aqua-hydroxo-M(III) trivalent metal species. Whether this is a general property of trans-aqua-hydroxo-M(II) species, or if it is specific for Mn(II) and/or to the seven-coordinate structures, remains to be seen and motivates future studies. In addition, an influence of the hydroxo ligand on the SOD activity of manganese(II) complexes could be evaluated for the first time as well. Compared with the mononuclear analogue, which is not able to form stable hydroxo species, our pH dependent studies on the SOD activity of the dinuclear amine complex have indicated that the hydroxo ligand may promote protonation and release of the product H(2)O(2), especially in solutions of higher pH values, by increasing its pK(a) value.

Water exchange on a molecular, purely inorganic cobalt-based water oxidation catalyst, [Co(4)(II)(H(2)O)(2)(α-P(1)W(9)O(34))(2)](10-) (1), in the catalytically relevant pH region (pH 6-10) is studied using (17)O-NMR spectroscopy and ultrahigh-resolution electrospray ionization mass spectrometry. The results are compared with those of the inactive [Co(II)(H(2)O)(1)Si(1)W(11)O(39)](6-) (2), which is stable in the same pH region. The results obtained provide mechanistic details of the elementary reaction step related to the water oxidation on homogeneous metal oxide catalysts under catalytically relevant conditions. It is shown that the structural integrity of 1 and 2 is maintained, no deprotonation of the aqua ligands on the Co(II) centers occurs, and the water exchange does not undergo any mechanistic changeover at the catalytic pH conditions. We have demonstrated that the water exchange process is influenced by the cluster environment surrounding the water binding sites and is fast enough to not be rate-limiting for the water oxidation catalysis.

In this work the rate constants (k(ex)) and the activation parameters (DeltaH(double dagger), DeltaS(double dagger), and DeltaV(double dagger)) for the water exchange process on Mn(III) centers have experimentally been determined using temperature and pressure dependent (17)O NMR techniques. For the investigations the Mn(III) porphyrin complexes [Mn(III)(TPPS)S(2)](n-) and [Mn(III)(TMpyP)S(2)](n+) (S = H(2)O and/or OH(-)) have been selected due to their high solution stability in a wide pH range, enabling the measurements of water exchange in the case of both diaqua and aqua-hydroxo complexes. We have experimentally demonstrated that the water exchange on Mn(III) porphyrins is a fast process (k(ex) approximately = 10(7) s(-1)) of an I(d) to I mechanism, strongly influenced by a Jahn-Teller effect and as such almost independent of a porphyrin charge and a trans ligand. This is also supported by our DFT calculations which show only a slight difference in an average Mn(III)-OH(2) bond found for a positively charged model porphyrin with protonated pyridine groups (2.446 A) and for a simple model without any substituents on the porphyrin ring (2.437 A). The calculated effective charge on the Mn center, which is significantly lower than its formal +3 charge (ca. +1.5 for diaqua; +1.4 for aqua-hydroxo), also contributes to its substitution lability. The herein presented results are discussed in connection to a possible fast exchanging substrate binding site in photosystem II and corresponding inorganic model complexes, as well as in the context of a possible inner-sphere catalytic pathway for superoxide dismutation on Mn centers.